期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 88, 期 -, 页码 844-855出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2020.03.022
关键词
Ageing; Leukotrienes; Microglia; Montelukast; Neuroinflammation; Pranlukast; Zileuton
资金
- National Natural Science Foundation of China [81903585, 81603113, 81573413, 81773714, 81273497]
- Natural Science Foundation of Jiangsu Province [BK20150705]
- Fundamental Research Funds for the Central Universities of China [2632017PT01]
5-lipoxygenase (ALOX5) is an enzyme involved in arachidonic acid (AA) metabolism, a metabolic pathway in which cysteinyl leukotrienes (CysLTs) are the resultant metabolites. Both ALOX5 and CysLTs are clinically significant in a number of inflammatory diseases, such as in asthma and allergic rhinitis, and drugs antagonizing the effect of these molecules have long been successfully used to counter these diseases. Interestingly, recent advances in 'neuroinflammation' research has led to the discovery of several novel inflammatory pathways regulating many cerebral pathologies, including the ALOX5 pathway. By means of pharmacological and genetic studies, both ALOX5 and CysLTs receptors have been shown to be involved in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative/neurological diseases, such as in Parkinson's disease, multiple sclerosis, and epilepsy. In both transgenic and sporadic models of AD, it has been shown that the levels of ALOX5/CysLTs are elevated, and that genetic/pharmacological interventions of these molecules can alleviate AD-related behavioral and pathological conditions. Clinical relevance of these molecules has also been found in AD brain samples. In this review, we aim to summarize such important findings on the role of ALOX5/CysLTs in AD pathophysiology, from both the cellular and the molecular aspects, and also discuss the potential of their blockers as possible therapeutic choices to curb AD-related conditions.
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